Early life exposure to chronic unpredictable stress induces anxiety-like behaviors and increases the excitability of cerebellar neurons in zebrafish.

Anxiety is a common emotional disorder in children. To understand its underlying mechanisms, chronic unpredictable stress (CUS) has been established as a stress model in zebrafish. By using the tall tank test, the stress response reliability could be improved in adult fish which has not been confirmed in larvae. In addition, the increasing evidences have shown that cerebellum plays important roles in anxiety. Whether CUS will affect cerebellar neuronal activity remains unknown. We found that CUS exposure to larvae (from 10 to 17 days post fertilization) induced anxiety-like behaviors and social cohesion impairments within 1-2 d after CUS, including a prolonged freezing time, an increased time spent at the bottom of tank, an increased thigmotaxis index, and an increased interindividual distance. Our results showed that the four behavioral tests were homogeneous, especially the tall tank test either anxiety-like behaviors or the basal locomotion. Furthermore, we found that CUS enhanced the excitability of cerebellar neurons, as the amplitude, frequency, time to peak and half-width of spontaneous firing significantly decreased, as well as the amplitude of excitatory post-synaptic current when compared with the control group. CUS also activated hyperpolarization-activated cyclic nucleotide-gated and potassium channels of cerebellar neurons. Multiple linear regression analysis showed that the total distance in bottom (tall tank test) was correlated positively with outward Na+-K+ currents (r = 0.848, P = 0.016), and the thigmotaxis index (open field test) correlated with action potential amplitude (r = 0.854, P = 0.030). Altogether, early life CUS transiently induced an anxiety-like behavior which could be more accurately assessed by combining the tall tank test with other behavior tests in young zebrafish. CUS increased the excitability of cerebellar neurons might provide new targets to treat emotional diseases such as anxiety.

Poly(I:C)-exposed zebrafish shows autism-like behaviors which are ameliorated by fabp2 gene knockout.

Introduction: Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders mainly representing impaired social communication. The etiology of ASD includes genetic and environmental risk factors. Rodent models containing ASD risk gene mutations or environmental risk factors, such as exposure to maternal inflammation, show abnormal behavior. Although zebrafish conserves many important brain structures of humans and has sophisticated and fine behaviors in social interaction, it is unknown whether the social behaviors of their offspring would be impaired due to exposure to maternal inflammation. Methods: We exposed zebrafish to maternal immune activation (MIA) by injection with polyinosinic:polycytidylic acid [poly(I:C)], and screened their behaviors through social behavioral tests such as social preference and shoaling behavior tests. We compared phenotypes resulted from different ways of poly(I:C) exposure. RNA sequencing was performed to explore the differential expression genes (DEGs). Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and protein-protein interaction (PPI) network analysis was performed with the detected DEGs to find the concentrated pathways. Finally, we knocked out the fatty acid-binding protein 2 (fabp2), a key node of the concentrated PPI network, to find its rescues on the altered social behavior. Results: We reported here that MIA offspring born to mothers injected with poly(I:C) exhibited impaired social approach and social cohesion that mimicked human ASD phenotypes. Both maternal exposure and direct embryo exposure to poly(I:C) resulted in activations of the innate immune system through toll-like receptors 3 and 4. RNA-sequencing results from MIA brain tissues illustrated that the numbers of overexpressed genes were significantly more than that of underexpressed genes. GO and KEGG analyses found that MIA-induced DEGs were mainly concentrated in complement and coagulation cascade pathways. PPI network analyses suggested that villin-1 (vil1) pathway might play a key role in MIA-induced ASD. Knockout of fabp2 in F0 zebrafish rescued the social behavior deficits in MIA offspring. Conclusions: Overall, our work established an ASD model with assessable behavior phenotype in zebrafish and provided key insights into environmental risk factor in ASD etiology and the influence of fabp2 gene on ASD-like behavior.

Effects of continuous positive airway pressure on elderly patients with obstructive sleep apnea: a meta-analysis.

OBJECTIVE: the aim of the study was to evaluate the efficacy of continuous positive airway pressure (CPAP) for the treatment of obstructive sleep apnea in the elderly. METHOD: a comprehensive search for qualified clinical trials was performed on April, 2016. Basic demographic information of enrolled subjects, study design, survival rate, cardiovascular events, quality of life scores, and neurocognitive data were extracted for analysis. RESULTS: A total of seven clinical trials were included in this meta-analysis, in which untreated elderly patients exhibited worse survival rate than those with CPAP (OR=2.22, 95% CI=1.64 to 3.01, P< 0.00001). Treated elderly patients exhibited less cardiovascular risk than those without CPAP (RR=0.49, 95% CI=0.36 to 0.66, P<0.00001) and a statistically significant improvement on all the domains of Quebec Sleepiness Questionnaire, supported by pooled weighted mean difference. Furthermore, CPAP treatment partially improved the cognitive functions. CONCLUSION: CPAP treatment achieves improvements in decreasing mortality and controlling cardiovascular events and exhibits few effects on neurocognitive function. Further large-scale, well-designed interventional investigation is needed.